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Johnson & Johnson: GPRC5DxCD3 bispecific antibody
Johnson & Johnson: GPRC5DxCD3 bispecific antibody. GPRC5DxCD3 bispecific antibody! Johnson & Johnson talentamab in the treatment of relapsed or refractory multiple myeloma: total remission rate 69%!
Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced the first human dose of talentamab (JNJ-64407564) for the treatment of relapsed or refractory multiple myeloma (R/R MM) at the 62nd Annual Meeting of the American Society of Hematology (ASH) Preliminary data for incremental research. The results showed that at the recommended phase 2 dose (RP2D) for subcutaneous (SC) administration, the overall response rate (ORR) of the talentamab treatment reached 69%.
talquetamab is a first-in-class bispecific antibody that simultaneously targets GPRC5D (a novel target for multiple myeloma) and CD3 (anti-cancer T cell surface receptor). GPRC5D (G protein coupled receptor C5 family subtype D) is highly expressed in multiple myeloma, and CD3 is involved in activating T cells. The results of preclinical studies in a mouse model showed that talentamab induces T cell-mediated killing of GPRC5D-positive multiple myeloma cells by recruiting and activating CD3-positive T cells, and inhibits tumor formation and growth.
Ajai Chari, director of clinical research for the Multiple Myeloma Project of the Mount Sinai Cancer Clinical Trials Office, said: “There is an urgent need to continue to innovate multiple myeloma treatment methods, especially for those who have received other therapies to relapse. Encouraging. The overall response rate and safety data from the Phase I study support further research into the monotherapy and combination therapy of talquetamab in a patient population with few treatment options.”
Dr. Yusri Elsayed, Global Head of Hematology Malignancies at Janssen Research and Development, said: “GPRC5D is a new target for the treatment of multiple myeloma. As a bispecific antibody, by targeting CD3 to bind to T cells, talquetamab is becoming an excessive prognosis. A potential treatment option for treating patients. Based on the preliminary efficacy, safety, pharmacokinetic and pharmacodynamic data provided today, we are committed to fully exploring the prospects of talentamab in the treatment of multiple myeloma.”
The phase I study announced at the meeting enrolled 157 patients with multiple myeloma (MM) who have received any existing therapies but have progressed or are intolerant. The median number of previous treatment options received is 6 types (range: 2-20), 87% are ineffective to the last treatment regimen, 82% are refractory to Class III drugs, and 33% are refractory to five types (for ≥2 immunomodulators, ≥2 Proteasome inhibitor (PI) and an anti-CD38 therapy are ineffective). The study is divided into two parts: dose escalation (part one) and dose extension (part two).
In the study, the therapeutic dose of talquetamab is: intravenous (IV) dose of 1-180μg/kg, subcutaneous (SC) dose of 5-800μg/kg. The results of the first part of the study showed that patients treated with talltaamab showed treatment responses in each dose group; at all doses, the median time from treatment to the first confirmation of response was 1 month (range: 0.2-3).
Preliminary results of subcutaneous (SC) and intravenous (IV) preparations show encouraging clinical activity against the GPRC5D target. The GPRC5D target is highly expressed on multiple myeloma cells and is related to poor prognostic factors. At the SC recommended phase 2 dose (RP2D), the overall response rate (ORR) was 69% (9/13), and 39% of patients achieved very good partial response (VGPR) or better.
The researchers determined that the RP2D for SC administration was 405μg/kg, and concluded that SC administration therapy may provide an opportunity for lower dosing frequency than IV formulations. Treatment response was observed in 6/9 of three types of refractory patients and 2/2 of five-fold refractory patients. The pharmacokinetic results indicate the target exposure level at the RP2D dose. When RP2D was 405 μg/kg SC, the pharmacodynamic data showed sustained T cell activation, cytokine production and redistribution.
In this study, the adverse event (AE) in the SC cohort with an incidence of ≥25% at RP2D dose was neutropenia (42%). After SC administration at the RP2D dose, 64% of patients observed cytokine release syndrome (CRS), all of which were low-grade, and there was no CRS event ≥3. The median occurrence of CRS after administration was 2 days, and the median duration of CRS was also 2 days. After SC administration at the RP2D dose, the incidence of neurotoxicity was 5%, and no patients had events ≥ Grade 3.